Dietary supplements containing extracts of cinnamon and methods of using same to enhance creatine transport

ABSTRACT

Materials derived from cinnamon can be administered orally to humans or animals for the purpose of controlling blood glucose as well improving glucose tolerance. Controlling glucose metabolism is essential for those with impaired glucose metabolism as is the case for those with Type II diabetes where insulin function is not properly functioning. Such administration can also be used for the purpose of enhancing nutrient transport for purposes of athletic performance and controlling bodyweight and body fat levels. Similarly related, such administration can also be used for the purpose of enhancing creatine transport into excitable tissues such as skeletal muscle. The material can be administered as extracts of cinnamon and can be administered in a variety of ways including capsules, tablets, powdered beverages, bars, gels or drinks.

FIELD OF THE INVENTION

[0001] The present invention is directed to dietary supplementscomprising cinnamon, or extracts thereof or derivatives of the extractsthereof, and to methods of using these dietary supplements to enhancenutrient transport and to promote weight loss, both in humans andanimals.

BACKGROUND

[0002] Type II diabetes is quickly becoming an epidemic in the UnitedStates. The increased incidence of Type II diabetes has been attributedto diets characterized by high fat intake and repeated ingestion ofrefined foods and sugars, coupled with low fiber and vegetable intake.Diet, along with the natural aging process, causes a deterioration inthe way in which the body metabolizes blood glucose. When the bodycannot properly metabolize blood glucose, a tendency to store glucose asfat typically occurs. This is one reason levels of body fat increasewith age. Diabetes is also known to be associated with a variety ofother ailments including heart disease, hypertension, and obesity. Thereis a known link between insulin resistance and increased visceraladiposity. Diabetes is also a leading cause of glaucoma and otherconditions related to a decrease in the quality of life.

[0003] It has long been known that natural and/or synthetic substancesmay aid in controlling blood glucose and enhancing nutrient transport.Such substances act by a variety of mechanisms. For example, somesubstances act by mimicking the effects of endogenous insulin and aretherefore capable of replacing endogenous insulin. Such substancesinclude synthetic insulin injections such as those which are routinelyprescribed to individuals with Type I diabetes. Other commonlyprescribed substances known to mimic the effects of insulin include thenaturally occurring compounds taurine, 4-hydroxyisoleucine, arginine,and vanadium. Although these compounds have been shown to work asinsulin mimetics by acting in the body to decrease serum blood glucoselevels, they have not been successfully developed into viable treatmentsfor disorders of glucose metabolism.

[0004] Still other substances act directly to increase what is termedinsulin sensitivity or glucose tolerance. Glucose intolerance forces thebody to generate additional insulin in an effort to lower blood glucose.This causes stress on the beta-cells of the pancreas and is thought tobe a key contributor to Type II diabetes. In a state of glucoseintolerance, the body mechanism for disposing of blood glucose is notfunctioning at its optimum level and therefore the system isinefficient. Substances which increase insulin sensitivity or glucosetolerance by assisting the body in returning to optimal levels of bloodglucose include alpha-lipoic acid, pinitol and myo-inositol. Thesesubstances cannot entirely replace the function of endogenous insulin,but work at the receptor level alongside endogenous insulin to increaseinsulin sensitivity or glucose tolerance. Here, the action is exerteddirectly on the Glut-4 receptor of the cell to trigger the cascadenormally caused by insulin that allows for the reduction in blood sugarvia the transport of nutrients into the cell.

[0005] In the past, chromium was thought to aid in weight loss bycontrolling blood glucose and preventing the deposition of fatty acids.However, its actions were greatly limited and its claims never came tofruition. Cinnamon, known for its high concentration of chromium, hasalso been used for the control of blood glucose. However, researchershave demonstrated that cinnamon's effects are not from chromium, butrather from a different class of compounds. One study by Kahn et al.compared the chromium levels of foods and spices including cinnamon, andfailed to find a correlation between chromium level and the level ofinsulin potentiation. (Biological Trace Element Research, 1990;24:183-188). A meta-analysis by Althuis et al. showed no associationbetween chromium and glucose or insulin concentrations. (Am. J Clin.Nutr., 2002; 76:148-55). A study by Broadhurst et al. has demonstratedthat cinnamon is a strong potentiator of insulin in comparison tovarious other herbs and spices. (J. Agric. Food Chem., 2000;48:849-852).

[0006] One particular extract of cinnamon, methyl hydroxy chalconepolymer (MHCP), shows promising data in the area of glucose control. Arecent study compared the effect of MHCP in 3T3-L1 adipocytes to that ofinsulin. (Jarvill-Taylor et al., J Am. College Nutr., 2001; 20:327-336).The results from that study support the theory that MHCP triggers theinsulin cascade and subsequent transport of nutrients. The study alsodemonstrated that MHCP treatment stimulated glucose uptake and glycogensynthesis to a similar level as insulin. The study further demonstratedthat treatment with endogenous insulin and MHCP resulted in asynergistic effect. Due to these conclusions it is suggested that MHCPmay prove to be a very valuable tool in the fight against diabetes,where insulin is present.

[0007] In addition to benefiting Type II diabetics, cinnamon may benefitindividuals with impaired glucose tolerance (i.e., pre-diabetics).Further, cinnamon has been shown to possess antioxidant activitiesrelated to lipid peroxidation. (Mancini-Filho et al., Bollettino ChimicoFarmaceutico, 1998; 37:443-47). Cinnamon can be used as a foodantioxidant and to enhance food palatability.

[0008] In broad terms, nutrient transport involves the deposit ofnutrients into various tissues. For example, after the insulin cascade,the Glut-4 transport system triggered by insulin drives nutrients suchas carbohydrates, amino acids (e.g., glutamine, arginine, leucine,taurine, isoleucine and valine) and creatine into skeletal tissue.Typically, water is driven into the cells at the same time.

[0009] Creatine is a natural dietary component primarily found in animalproducts. In the body, creatine is stored predominantly in skeletalmuscle, and mostly in the form of phosphorylated creatine, but also inits free state. Total creatine content of mammalian skeletal muscle(i.e., creatine and phosphorylated creatine) typically varies from about100 to about 140 mmol/kg. The level of creatine and phosphorylatedcreatine present in skeletal muscle can be increased through dietarysupplementation with creatine.

[0010] The fuel for all muscular work in the body is adenosinetri-phosphate, or ATP. During intense exercise, ATP is utilized veryrapidly. The body does not store much ATP in muscle so other substancesmust be broken down in order to replenish the ATP that is rapidly brokendown during exercise. If the ATP is not replenished, fatigue occurs andforce/power production declines. Of all the substances in the body thatcan replenish ATP, the fastest is phosphorylated creatine. Thus, theprimary function of phosphorylated creatine in muscle is to buffer ATPby preventing decreases in ATP during exercise.

[0011] Creatine is taken up into tissues, such as skeletal muscle, bymeans of an active transport system that typical involves an insulindependent pathway. In a study by Stengee et al., insulin was co-infusedalong with creatine supplementation. (Am. J Physiol., 1998;275:E974-79). The results of this study indicated that insulin canenhance creatine accumulation in muscle, but only if insulin levels arepresent at extremely high or supra-physiological concentrations. Stengeeet al. refers to a previous study by Green et al. which involvedexperimentation with ingestion of creatine in combination with acarbohydrate-containing solution to increase muscular uptake of creatineby creating physiologically high plasma insulin concentrations. Stengeeet al. reports that Green et al. had found the quantity of carbohydratenecessary to produce a significant increase in creatine uptake, ascompared to creatine supplementation alone, was close to the limit ofpalatability.

[0012] Thus, there exists a need in the art for a viable method ofincreasing the uptake of creatine into mammalian tissue, such asskeletal muscle. Further, there exists a need in the art for a dietarysupplement whose administration at normal physiological concentrationswould effect such an increase in creatine uptake.

SUMMARY

[0013] Disclosed herein is: (a) a dietary supplement comprisingcinnamon, or an extract thereof or a derivative of the extract thereofand a nutrient, or a derivative or a precursor thereof, with or withouta carbohydrate; and (b) methods of increasing the uptake of nutrients inmammalian muscle, enhancing nutrient transport, and enhancing athleticperformance comprising administration of said dietary supplement.

[0014] Accordingly, it is an object of the invention to provide a methodand a dietary supplement which will enhance the uptake of nutrients intomammalian muscle. More specifically, it is an object of the invention toprovide a method and a dietary supplement which will enhance the uptakeof creatine into skeletal muscle. It is a further object of theinvention to provide a method and a dietary supplement that triggers aninsulin dependent pathway to enhance the uptake of creatine intoskeletal muscle. It is a still further object of the invention toprovide a method and a dietary supplement that achieves these objectswhen administered in physiologically acceptable amounts.

[0015] Also disclosed herein is: (a) a dietary supplement comprisingcinnamon, or an extract thereof or a derivative of the extract thereofand (b) methods of losing weight and reducing body fat comprisingadministration of said dietary supplement.

[0016] Accordingly, it is also an object of the invention to provide amethod and a dietary supplement which will promote weight loss and bodyfat reduction.

[0017] Other objectives, advantages and features of the invention willbecome apparent from the following detailed description, and from theclaims.

BRIEF DESCRIPTION OF THE PREFERRED EMBODIMENT

[0018] The creatine-containing dietary supplements of the inventioncomprise cinnamon, or an extract thereof or a derivative of the extractthereof and creatine, or a derivative or a precursor thereof, with orwithout a carbohydrate.

[0019] Additionally, the body fat reduction and weight loss dietarysupplements of the invention comprise cinnamon, or an extract thereof ora derivative of the extract thereof.

[0020] Cinnamon is one of the world's most popular spices. Cinnamoncontains over one hundred different chalcones within it. Chalcones are atype of polyphenol or flavonoid. These chalcones may be extracted fromcinnamon and isolated, and, optionally, derivatized. One chalcone whichcan be extracted from cinnamon is the phytochemical methyl hydroxychalcone polymer, or MHCP. In a preferred embodiment of the invention,the dietary supplement includes MHCP.

[0021] The isolation of phytochemicals from cinnamon follows the generalprocess of aqueous extraction followed by centrifugation to removenon-soluble compounds. Specifically, MHCP and other water-solublepolyphenol polymers can be extracted from cinnamon using the followingprocess: 5 g cinnamon and 100 ml 0.1 N acetic acid are combined andautoclaved for 15 minutes. The resultant mixture is cooled, thencentrifuged and the precipitate discarded. Four volumes of ethanol/0.1 Nacetic acid are added to the supernatant and the mixture is storedovernight at 4 C°. The mixture is screened through a filter and thenintroduced onto an LH-20 column and washed with 600 ml ethanol/0.1 Nacetic acid. The desired fraction is then eluted with a 1:1 mixture ofacetonitrile and 0.2 N acetic acid. The eluent is then concentrated andintroduced onto a HPLC column at 275 nm.

[0022] The chemical name for creatine is methylguanidino acetic acid.This is the free form of creatine. Known creatine derivatives includecreatine monohydrate and other hydrates, creatine salts such as creatinecitrate, creatine esters, phosphorylated creatine, and creatinepyruvate. Known creatine precursors include glycocyamine orGuanidineacetic Acid and the amino acids arginine, glycine, andmethionine. In a preferred embodiment of the invention for thecreatine-containing dietary supplements, the dietary supplement includescreatine monohydrate.

[0023] The optional carbohydrate in the creatine-containing dietarysupplements of the invention include simple sugars such as themonosaccharides glucose and dextrose.

[0024] Typical formulations of creatine-containing dietary supplementsaccording to the invention include: dietary supplements containing fromabout 0.1 mg to about 100 mg of cinnamon extract or cinnamon extractderivative per gram of dietary supplement; dietary supplementscontaining from about 1 mg to about 900 mg of creatine or creatinederivative or creatine precursor per gram of dietary supplement, andpreferably from about 50 mg to about 125 mg of creatine or creatinederivative or creatine precursor per gram of dietary supplement; dietarysupplements containing from about 1 mg to about 950 mg of carbohydrateper gram of dietary supplement, preferably from about 400 mg to about900 mg of carbohydrate per gram of dietary supplement, and morepreferably from about 500 mg to about 800 mg of carbohydrate per gram ofdietary supplement.

[0025] Typical formulations of the body fat reduction and weight lossdietary supplements of the invention include dietary supplementscontaining from about 1 mg to about 1,000 mg of cinnamon extract orcinnamon extract derivative per gram of dietary supplement.

[0026] Typical daily dosages of the creatine-containing dietarysupplements of the invention are about 10 mg to about 10,000 mg ofcinnamon extract or cinnamon extract derivative and about 100 mg toabout 25,000 mg of creatine or creatine derivative or creatineprecursor, and preferably about 500 mg to about 10,000 mg of creatine orcreatine derivative or creatine precursor. Generally, thecreatine-containing dietary supplements of the invention areadministered in an amount of from about 200 mg to about 500 g per day.

[0027] Typical daily dosages of the body fat reduction and weight lossdietary supplements of the invention are about 10 mg to about 10,000 mgof cinnamon extract or cinnamon extract derivative. Generally, the bodyfat reduction and weight loss dietary supplements of the invention areadministered in an amount of from about 100 mg to about 500 g per day.

[0028] The dietary supplements of the invention are orally administeredand can be in the form of capsules, tablets, powdered beverages, bars,gels or drinks.

[0029] Administration of the dietary supplements of the invention willmimic the effects of insulin and will decrease glucose intolerance,thereby increasing the efficiency of insulin. As a result,administration of the creatine-containing dietary supplements of theinvention will enhance the transport of creatine into tissues such asskeletal muscle. The increase in the amount of creatine storage in themuscle can be measured by muscle biopsy. Upon administration of thecreatine-containing dietary supplements of the invention for a period ofdays (e.g., for as little as 4 days and as many as 30 days), the totalcreatine content of skeletal muscle (i.e., free and phosphorylatedcreatine) will increase from about 10% to about 40% where typical levelsof total creatine in skeletal muscle prior to administration are betweenabout 100 to about 140 mmol/kg of dry muscle.

[0030] Administration of the body fat reduction and weight loss dietarysupplements of the invention, particularly to individuals with impairedglucose tolerance, will have the effect of restoring optimal glucosefunctioning, therefore lessening the likelihood of adipose storage, andleading to a reduction in body fat and weight.

EXAMPLE 1

[0031] Four subjects (males ages 18-45 yr) consumed one serving of adietary supplement as described herein four times per day for five days.Each serving of the dietary supplement is approximately 96 g andincludes the following active ingredients: Compound Amount creatinemonohydrate about 7.5 g creatine magnesium chelate about 2.5 g CinnulinPF ™ (a source of about 200 mg water-soluble extracts of cinnamon)carbohydrates (dextrose, maltodextrin, about 69 g trehalose and maltose)

[0032] Each approximate 96 g serving is mixed with 8 ounces of water toprovide a liquid drink for consumption. The subjects followed aweight-lifting regime on four out of the five days. On these fourworkout days, the subjects consumed one serving of the dietarysupplement 60 minutes before working out and another serving of thedietary supplement immediately after finishing working out. The subjectsconsumed the remaining two servings of the dietary supplement withcarbohydrate-containing meals. On the one non-workout day, the subjectsconsumed one serving of the dietary supplement every four hours. Thisstudy demonstrated that administration of the dietary supplement causedan average 20% increase in strength among the subjects, as measured bybenchpress (number of repetitions) to failure.

[0033] The examples and embodiments set forth in the present applicationare provided only to illustrate various aspects of the invention andadditional embodiments and advantages of the dietary supplements andmethods of the present invention will be apparent to those skilled inthe art.

What is claimed is:
 1. A dietary supplement comprising: a. cinnamon, oran extract of cinnamon, or a derivative thereof, and b. creatine, or aderivative or a precursor thereof.
 2. The dietary supplement of claim 1wherein element (a) comprises a water soluble extract of cinnamon, or aderivative thereof.
 3. The dietary supplement of claim 1 wherein element(a) comprises a polymer derived from cinnamon, preferably methyl hydroxychalcone polymer, or a derivative thereof.
 4. The dietary supplement ofclaim 1 wherein element (b) comprises a creatine hydrate or a creatinesalt.
 5. The dietary supplement of claim 1, wherein element (b)comprises creatine monohydrate.
 6. The dietary supplement of claim 1,wherein element (b) comprises creatine magnesium chelate.
 7. The dietarysupplement of claim 1, wherein element (b) comprises creatinemonohydrate and creatine magnesium chelate.
 8. The dietary supplement ofclaim 1, wherein element (b) is selected from the group consisting ofglycocyamine, guanidinopropionic acid, trimethyl glycine and s-adenosylmethionine.
 9. The dietary supplement of claim 1, further comprising atleast one carbohydrate.
 10. The dietary supplement of claim 9, whereinthe carbohydrate is selected from the group consisting of dextrose,maltose, maltodextrin and trehalose.
 11. The dietary supplement of claim1 wherein element (a) is present in an amount from about 0.1 mg to about100 mg per gram of dietary supplement and element (b) is present in anamount from about 10 mg to about 900 mg per gram of dietary supplement.12. The dietary supplement of claim 11 further comprising carbohydratespresent in an amount of from about 1 mg to about 950 mg per gram ofdietary supplement.
 13. A dietary supplement for oral administration,comprising from about 100 mg to about 25,000 mg of creatine or acreatine derivative or a creatine precursor and from about 10 mg toabout 2,000 mg of a water-soluble extract of cinnamon or a derivativethereof.
 14. The dietary supplement of claim 13 wherein administrationof said supplement in an amount from about 200 mg to about 500 g per dayfor a period of 4 to 30 days provides an increase in total creatinecontent of skeletal muscle from about 10 to about 56 mmol/kg dry muscle.15. A dietary supplement for oral administration, comprising about 2 mgwater-soluble cinnamon extracts per gram of dietary supplement and about78 mg creatine monohydrate per gram of dietary supplement.
 16. Thedietary supplement of claim 15, further comprising about 26 mg ofcreatine magnesium chelate per gram of dietary supplement.
 17. Thedietary supplement of claim 15, further comprising about 719 mg ofcarbohydrates per gram of dietary supplement.
 18. The dietary supplementof claim 17, wherein the carbohydrates comprise dextrose, maltose,maltodextrin and trehalose.
 19. A method of increasing the uptake ofcreatine in skeletal muscle, comprising the step of ingesting thedietary supplement of claim
 1. 20. A method of enhancing athleticperformance, comprising the step of ingesting the dietary supplement ofclaim 1.